Device System And Method For Tissue Displacement Or Separation

ABSTRACT

A tissue displacement/separation device is provided. The device includes a bladder which is expandable between a first tissue and a second tissue of a body. The bladder has an expanded shape which is selected capable of displacing or separating the first tissue from the second tissue in a manner suitable for protecting the first tissue from an effect of a treatment applied to the second tissue.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a device, system and method for tissuedisplacement/separation and, more particularly, to a tissuedisplacement/separation device which can be used to protect healthytissue from effects of treatment on adjacent treated tissues and yetminimize the physiological impact of displacement on the healthy tissue.

Removal or treatment of pathological tissue such as cancer or anymalignant or benign growth or tumor caused by abnormal and uncontrolledcell division can be effected in any one of several well knownapproaches.

The most common form of treatment is surgery, followed by radiation(external or internal), chemical and thermal therapies. Examples ofradiation therapies include but are not limited to external radiationbeam therapy and interstitial brachytherapy, a technique in whichradioactive sources are placed into the prostate gland, deliveringradiation from within the prostate.

Thermal treatment approaches include but are not limited to cryotherapyand thermal ablation. In thermal ablation, a balloon or catheter filledwith hot water is used to ablate target tissues. Cryosurgery, on theotherhand utilizes liquid nitrogen or argon gas expansion to injuretissue and is most often used when a tumor is small and cannot beremoved using surgery.

Chemical ablation therapy includes use of a variety of chemical agentsthat kill cells exposed thereto. Chemical ablation utilizes chemicalagents such as ethanol or hyperosmolar saline which are capable ofcausing necrosis to tissue exposed thereto.

Examples of other therapies that can be used for treatment include radiofrequency ablation (RFA), a technique that employs high-energy radiofrequency energy to destroy inoperable tumors and High Intensity FocusedUltrasound (HIFU), or Focused Ultrasound (FUS) which can be used torapidly kill tissue such as tumors and to stop internal bleeding bycauterizing injured organs or blood vessels.

The above described treatments approaches can be practiced individuallyor in combination as adjuvant therapy. In any case, each of the abovetherapeutic approaches carries some degree of risk of injury to healthytissues.

For example, during surgery, use of surgical instruments in small, tightspaces can lead to inadvertent tissue injury. Radiation therapy orlocalized release of chemical substances results in an intensitygradient between the treated tissue and healthy tissue and radiation orchemical injury to healthy tissues. As a result, the total energy orchemical dose for local treatment that can be applied to a tissue islimited by the dose that is inevitably transmitted to healthy adjacenttissues. Moreover, some tissues and organs are more sensitive toradiation and chemical damage than others and thus treatment of tissueadjacent to such tissues and organs can be severely limited.

Thus, there is a great need for an efficient, easy way to shield healthytissues from the harmful effects of treatment on adjacent pathologicaltissues, while applying a relatively high and more efficient dose to thepathological tissue. Presently there are a few approaches suitable forseparating healthy tissue from pathological/diseased tissue duringtreatment:

For example, U.S. Pat. No. 5,641,505 describes a material which can beused for tissue separation. The material comprises a porous flexiblesheet or tube of a protein-free bioresorbable polymer having pores,which permits the passage of water and salts through the sheet or tubewhile restricting the passage of cells and other tissue particles. Thisdevice is limited in that use thereof in radiation or chemical therapywill lead to undesirable exposure of healthy tissue to radiation energyand chemical agents.

U.S. Pat. No. 5,733,316 discloses a method of providing thermal therapyto prostate tissue of a patient which includes inserting a mechanicalseparator or infusing a fluid, to separate human tissue to be treated,from non-target tissue, thereby providing thermal insulation and otherbeneficial effects, and applying the thermal therapy to the targettissue. The method is applied by locating the fluid infusing device at alocation adjacent a portion of the patient's prostate and the patient'srectum to provide passage of a volume of a fluid from the device totarget location without a containment structure. This approach islimited in that it cannot be used to displace tissue rather just infuseit with a liquid.

U.S. Pat. Application publication No. 20020147386 discloses a method anda device for stabilizing and retracting tissue during surgery, inparticular internal tissue. Patches of material, preferablybiodegradable, are adhered to tissue surfaces, by manipulation of thepatches, for example directly with forceps, or via sutures attached tothe patches, tissues can be retracted or otherwise manipulated withminimal trauma to the tissues. While this approach might be useful insome cases, it does not enable rapid uniform tissue displacement.

U.S. Pat. Application publication No. 20040094162 discloses the use of afiller to space a first tissue from a second tissue. Although thisapplication described expandable devices such as balloons and sponges,it does not describe devices which can apply uniform pressure on thedisplaced tissue.

Thus, although prior art tissue separation approaches are capable ofphysically separating healthy tissue from treated tissue, and as aresult at least partially shielding healthy tissue from the harmfuleffects of treatment, prior art approaches suffer from several inherentlimitations the most prominent of which being an inability to uniformlydisplace tissue or retain a stable shape throughout the medicalprocedure.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, a tissue displacement/separation device which canbe utilized to protect healthy tissue from the harmful effect oftreatment conducted on an adjacent pathological tissue while minimizingany harmful effects on healthy tissue that may be generated bydisplacement thereof.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided atissue displacement/separation device comprising a bladder beingexpandable between a first tissue and a second tissue of a body, thebladder having an expanded shape being selected capable of displacing orseparating the first tissue from the second tissue in a manner suitablefor protecting the first tissue from an effect of a treatment applied tothe second tissue.

According to yet another aspect of the present invention there isprovided a tissue displacement system comprising: (a) a bladder beingexpandable between a first tissue and a second tissue of a body, thebladder having an expanded shape being selected capable of displacingthe first tissue from the second tissue in a manner suitable forprotecting the first tissue from an effect of a treatment applied to thesecond tissue; and (b) a guide being detachably attached to the bladderand being for introducing the bladder into a tissue.

According to further features in preferred embodiments of the inventiondescribed below, the bladder is designed capable of fluid expansion.

According to still further features in the described preferredembodiments the expanded shape of the bladder is selected from the groupconsisting of a pear shape, a fusiform shape, a discoid shape, aflattened shape, a triangular shape, a flattened cylindrical shape andany shape capable of displacing target tissue while minimizing injurythereto.

According to still further features in the described preferredembodiments the expanded shape of the bladder is selected capable ofuniformly displacing or separating the first tissue from the secondtissue.

According to still further features in the described preferredembodiments the expanded shape is further selected so as to minimizepressure and/or contact damages imposable by the bladder to the firsttissue and/or the second tissue.

According to still further features in the described preferredembodiments the bladder is designed expandable via fluid filling.

According to still further features in the described preferredembodiments the bladder is designed expandable via an element capable ofassuming a coiled rigid state.

According to still further features in the described preferredembodiments the bladder is composed of biodegradable material.

According to still further features in the described preferredembodiments the bladder comprises a thermal insulating/reflectingmaterial.

According to still further features in the described preferredembodiments the bladder comprises radiation shielding material.

According to still further features in the described preferredembodiments the bladder comprises a transilluminative substance.

According to another aspect of the present invention there is provided Amethod of protecting a first tissue from an effect of a treatmentapplied to a second tissue comprising: (a) positioning an expandablebladder between the first tissue and the second tissue; and (b)expanding the bladder to an expanded shape thereby displacing orseparating the first tissue from the second tissue and as a resultprotecting the first tissue from the effect of the treatment applied tothe second tissue.

According to still further features in the described preferredembodiments the treatment is selected from the group consisting ofthermal treatment, radiation treatment and drug treatment.

According to still further features in the described preferredembodiments the first tissue is selected from the group consisting ofprostate, urinary bladder, rectum, vaginal wall, uterine cervix, uterus,kidney, liver, lung, mediastinum, mammary gland and the like.

According to still further features in the described preferredembodiments the positioning is effected via a guide.

According to still further features in the described preferredembodiments the expanding is effected by filling the bladder with afluid.

According to another aspect of the present invention there is provided Amethod of forming a seamless bladder comprising: (a) providing a bladdertemplate produced from material soluble in a first liquid; (b) coatingthe template with a solution of a polymer insoluble in the first liquidto thereby generate a polymeric coat on the template; and (c) exposingthe template and polymeric film to the first liquid thereby dissolvingthe template and releasing the polymeric film and forming the seamlessbladder.

According to still further features in the described preferredembodiments the first liquid is a hydrophilic liquid.

According to still further features in the described preferredembodiments the material soluble in a first liquid is gelatin or agar.

According to still further features in the described preferredembodiments the polymer can be a biodegradable polyester made fromhydroxyl alkanoic acids, polyorthoesters, polyphosphazenes,polyphosphate esters, polyanhydrides and copolymers and blends thereof.Of particular interest are homo and copolyesters made from lactic acid,glycolic acid and caprolactone. The preferred polymers are those thatare in clinical use that have already shown to be safe with predictablebiodegradability, i.e. polylactide, poly(lactide-glycolide),poly(lactide-caprolactone) and polycaprolactone.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a device system and methodwhich can be easily used in separating/displacing and thus protectinghealthy tissues from the harmful effects of treatment applied toadjacent pathological tissue.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 a illustrates one embodiment of the tissuedisplacement/separation device of the present invention.

FIG. 1 b is a side view of the device of FIG. 1, showing the bladder ina collapsed (rolled) state.

FIG. 1 c is a side view of the device of FIG. 1, showing the bladder inan expanded state.

FIG. 1 d illustrates an embodiment of the tissue displacement/separationdevice of the present invention in which the bladder is expanded usingan elongated member capable of assuming a coiled state.

FIG. 1 e illustrates the tissue displacement/separation system of thepresent invention.

FIG. 2 illustrates the dipping method used to fabricate the seamlessbladder utilized by the device of the present invention.

FIGS. 3 a-c illustrate prostate-rectal tissue (FIG. 3 a) and anembodiment of the device of the present invention (FIG. 3 b—front view;FIG. 3 c—side view) particularly suitable for use in a treatmentprocedure applied within this tissue region (noted by arrow).

FIGS. 4 a-c illustrate liver/gallbladder tissue (FIG. 4 a) and anembodiment of the device of the present invention (FIG. 4 b—front view;FIG. 4 c—side view) particularly suitable for use in a treatmentprocedure applied within this tissue region (noted by arrows).

FIGS. 5 a-c illustrate colorectal tissue (FIG. 5 a) and an embodiment ofthe device of the present invention (FIG. 5 b—front view; FIG. 5 c—sideview) particularly suitable for use in a treatment procedure appliedwithin this tissue region (noted by arrow).

FIGS. 6 a-e illustrate uterine tissue (FIG. 6 a) and an embodiment ofthe device of the present invention (FIGS. 6 b, d—front view; FIGS. 6 c,e—side view) particularly suitable for use in a treatment procedureapplied within this tissue region (noted by arrows).

FIGS. 7 a-c illustrate rectal tissue (FIG. 7 a) and an embodiment of thedevice of the present invention (FIG. 7 b—front view; FIG. 7 c—sideview) particularly suitable for use in a treatment procedure appliedwithin this tissue region (noted by arrow).

FIGS. 8 a-c illustrate thoracic tissue (FIG. 8 a) and an embodiment ofthe device of the present invention (FIG. 8 b—front view; FIG. 8 c—sideview) particularly suitable for use in a treatment procedure appliedwithin this tissue region (noted by arrows).

FIGS. 9 a-c illustrate breast tissue (FIG. 9 a) and an embodiment of thedevice of the present invention (FIG. 9 b—front view; FIG. 9 c—sideview) particularly suitable for use in a treatment procedure appliedwithin this tissue region (noted by arrows).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a device system and method which can be usedto protect a first tissue from the effect of treatment conducted on asecond and adjacent tissue.

The principles and operation of the present invention may be betterunderstood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Treatment of body tissue via local release of chemical substances orprovision of a radiation dose results in chemical/radiation gradientbetween the treated tissue and normal tissue. Therefore, the totalradiation or chemical dose which can be applied to a tissue is limitedby the dose that is inevitably transmitted to normal adjacent tissues.

To traverse this treatment limitation, several devices have been adaptedfor tissue protection during localized treatment of body tissues (see,the background section for examples). Although the above described priorart devices can be used to protect a tissue region from the harmfuleffects of a treatment conducted on an adjacent tissue, such deviceseither lack the shape necessary for effective tissue protection or arenot effective in reducing the physiological impact on the tissuedisplaced.

Thus, according to one aspect of the present invention there is provideda tissue displacement/separation device which can be utilized to protecta body tissue from the harmful effects of treatment, such as thermal orradiation treatment.

As used herein the term “displacement/separation” refers to eithermoving one tissue away from another or by filling a void between tissueswith a physical barrier.

The device of the present invention includes a bladder which isexpandable between a first tissue and a second tissue of a body of asubject (preferably human). As used herein, the terms “first tissue” and“second tissue” can denote two tissue types (for example,prostate-rectum, uterus-rectum, uterus-small bowels, urinarybladder-uterus, ovary-bowels uterus-urinary bladder, liver-gallbladder,lung-mediastinum, mediastinum-lung, mammary gland-thoracic wall,esophagus-spine, thyroid-blood vessels, thyroid-pharynx and larynx,small bowels and large bowels-retroperitoneum, kidney-liver,pancreas-stomach, pancreas-spine, stomach-liver, stomach-spine, etc) ordifferent tissue regions of the same tissue type. It will be appreciatedthat in the latter case, the two tissue regions can be naturallyadjacent and attached by fibroconjunctive tissue (e.g., lobes of a lung)and can be separated by the introduction of an incision.

In any case, the device of the present invention is designed such thatan expanded shape thereof is selected capable of displacing the firsttissue from the second tissue. Such physical separation optionallycombined with a barrier effect of the device protects the first tissuefrom an effect of a treatment applied to the second tissue.

As used herein, the term “treatment” when used in context of the firstand second tissues denotes any treatment which can be harmful to theuntreated tissue (e.g. first tissue). Examples of treatments includeradiation treatment, such as, for example, external radiation therapyusing gamma irradiation, high energy photon beam therapy, electron beamtherapy, proton beam therapy, neutron beam therapy, heavy particle beamtherapy, conformal 3d radiation therapy, intensity modulated radiationtherapy (IMRT), interstitial brachytherapy or any combination thereof.Treatment can also include drug treatment (local) such as alcohol tissueablation or hyperosmolar ablation using NaCl crystals or hyperosmolarsolution or physical tissue manipulation (e.g. dissection).

Thus, the present invention provides a device which is useful inprotecting tissue from the harmful effects of various types oftreatments including, but not limited to, externally provided radiationtherapy such as, ionizing radiation, or non-ionizing radiation(microwave therapy, radiofrequency therapy, high intensity focusedultrasound therapy, etc), or interstitial therapy such as, for example,interstitial brachytherapy, interstitial thermal ablation, contactthermal ablation by hot liquid, high intensity focused ultrasound,thermoregulated rods, interstitial laser therapy with or withoutphotodynamic agents, cryotherapy, interstitial chemical ablation,localized chemotherapy, etc. Such a device is also useful in invasivetreatments, such as, surgical extirpation, when blunt dissection andseparation of tissue can be difficult and can result in inadvertentinjury to adjacent organs.

It will be appreciated that any number of the present device can beutilized to fill complex spaces in order to displace one tissue fromanother. The devices might be interconnected in order to maintain afunctional protective structure. Multi-device structures might besuitable for physical separation in the peritoneal cavity wherein someof the interconnected devices serve as anchors to the body wallpreventing movement and migration of the structure.

Referring now to the drawings, FIGS. 1 a-c illustrates one embodiment ofthe device of the present invention which is referred to herein asdevice 10.

Device 10 includes a bladder 12 which can be constructed out of anybiocompatible material. As used herein the term bladder refers to anychamber having an inner volume when expanded and substantially no innervolume when collapsed. Although FIGS. 1 a-c illustrate a flat balloonshape having an expanded state length L (FIG. 1 a e.g. from 1 to 20 cm),an expanded state width W (FIG. 1 a e.g. from 1 to 20 cm) and anexpanded state thickness T (FIG. 1 c e.g. from 1 to 10 cm), it will beappreciated that bladder 10 can be fabricated in any shape suitable foruniform tissue displacement thus minimizing any localized pressure onthe displaced tissue. Examples of bladder 12 shapes include, but are notlimited to, a pear shape, a fusiform shape, a discoid shape, a flattenedshape, a triangular shape and a flattened cylindrical shape.

Reducing or minimizing localized pressure on displaced tissue isimportant since it ensures that displaced tissue is supplied with ampleblood flow and thus reducing the chances of localized ischemia. It willbe appreciated that by selecting a shape that ensures such uniformpressure on the displaced tissue, the present device overcomes thedeficiencies of prior art balloon-shaped displacement devices (e.g. U.S.Pat. No. 6,852,095) which can generate non-uniform pressure on displacedtissue (in particular soft tissues) and thus can lead to localizedischemia especially in long term procedures.

Examples of various bladder shapes which can be utilized by device 10 ofthe present invention are provided hereinbelow and in the Examplessection which follows.

Device 10 can be constructed from any biocompatible material including,but are not limited to, polymers, such as, biodegradable polyesters madefrom hydroxyl alkanoic acids, polyorthoesters, polyphosphazenes,polyphosphate esters, polyanhydrides and copolymers and blends thereof.Of particular interest are homo and copolyesters made from lactic acid,glycolic acid and caprolactone. The preferred polymers are those thatare in clinical use and have already shown to be safe with predictablebiodegradability, i.e. polylactide, poly(lactide-glycolide),poly(lactide-caprolactone) and polycaprolactone. The selected polymersshould fit the desired mechanical and physical stability of bladder 12in vivo. A biodegradable polymer that retains its mechanical andphysical properties when designed as a thin layer bladder, for at least2 months is utilized to produce a bladder which needs to retain itsmechanical and physical properties for two months in the body. Inaddition, the polymers should be film forming and flexible enough toenable folding of bladder 12 into a compact configuration that can beinserted within a tube that serves as dispenser for device 10 in vivo.The properties of the polymer compositions can be tailored to fit anyrequirements by either blending various polymers or mixing the polymerwith hydrophobic or hydrophilic additives that alter the polymerproperties. Such additives can be plasticizers that increase theflexibility of bladder 12, hydrophilic components such as poly(ethyleneglycol) and minerals that increase hydrophilicity and serve as poremaking agents. Hydrophobic components can be triglycerides, fatty acidsand esters and other biodegradable polymers. The polymer structure andmolecular weight play a significant role in designing the desiredproperties of the polymer composition.

FIG. 1 b illustrates bladder 12 in a collapsed (e.g. rolled) state whichis suitable for delivery using minimally invasive techniques (furtherdescribed hereinbelow). FIG. 1 c illustrates bladder 12 in an expandedstate which is capable of effecting tissue displacement or separation.

One suitable approach for fabricating device 10 from biodegradablepolymer solutions is provided in Example 1 of the Examples sectionhereinbelow. In the approach described, bladder 12 is constructed as aseamless structure by dipping a water soluble expanded bladder templatein an organic polymeric solution and removing the formed polymericbladder from the template by dissolving the template in water.

Device 10 can include a bioadhesive coating or any other physicalmechanism which can decrease its mobility within the insertion site.This feature is important to minimize movement of device 10 from thesite of application and thus guarantee optimal protection for thenon-treated tissue.

Suitable bioadhesives include as carboxymethyl cellulose (CMC) andsimilar bioadhesive that are allowed for use in humans. CMC may beapplied as dry film onto bladder 12. Following insertion and absorptionof water such a film develops adhesive properties towards tissue.Bladder 12 can be configured with various surface structures such aspimples, grooves, bumps, microhooks, ridges or any combination thereofsuch that when expanded a friction between bladder 12 surface anddisplaced tissue is increased without affecting the functionality of thedevice.

Expansion of bladder 12 is conducted in-tissue following insertion andpositioning of device 10. Such insertion and positioning can be effectedby using a guide (a suitable guide is further described hereinbelow withrespect to FIG. 1 d). Following expansion such a guide can be keptattached to device 10 during short term procedures in which treatment isprovided over a course of hours (e.g. thermal ablation) or it can bedetached therefrom during longer procedures in which treatment isprovided over a course of days, weeks or even months (e.g. long termradiation or interstitial procedures).

In the latter case, device 10 is preferably constructed from abiodegradable material such that device 10 degrades and is absorbed bythe body over a predetermined time period or following absorption of apredetermined dose amount of treatment (e.g., radiation). To enablebiodegradation, device 10 is constructed from polymers which arebiocompatible and bioabsorbable, and yet posses mechanical propertiessuitable for maintaining the desired in-tissue shape. Such polymers canbe prepared by synthetic or natural methods as long as the polymer isprovided in a sufficiently pure form suitable for use in body tissues.

The polymers may be prepared from any combination of monomeric units orfrom natural semi-synthetic and synthetic biodegradable polymers andcompositions. These units must, however, be capable of biodegrading invivo to non-toxic components, which can be excreted or furthermetabolized.

The combination of units in the polymer must also be biocompatible, andnot elicit an undesirable biological response upon implantation ofdevice 10. The polymer may be biodegraded in vivo via hydrolysis,enzymatic cleavage, cell-mediated degradation, or by any otherbiologically mediated process. Since the need for tissue displacementmay vary depending on the type and duration of treatment, it isdesirable to have polymers with a range of degradation rates as well asa range of different properties. Generally, however, preferred polymerswill degrade in a matter of weeks to months, preferably less than oneyear. Examples of suitable biodegradable polymers which can be used tofabricate device 10 include, but are not limited to, biodegradablepolyesters such as, polylactide, poly(lactide-glycolide),poly(lactide-caprolactone) and polycaprolactone.

Preferably, the polymer is a polyester constructed from a hydroxy acidmonomers. The hydroxy acid may optionally contain other functionalgroups and be substituted at any position, including heteroatoms betweenthe hydroxy and acid groups. These hydroxy acids may be polymerizedusing synthetic methods or preferably using biological methods. In thelatter case, the hydroxy acids may be derived in vivo from a non-hydroxyacid source. Suitable methods for preparing polyesters are described inWilliams, S. F. and Peoples, O. P. CHEMTECH, 26:38-44 (1996), Hocking,P. J. and Marchessault, R. H. “Biopolyesters”, G. J. L. Griffin, Ed.,“Chemistry and Technology of Bioabsorbable Polymers,” Chapman and Hall,London, 1994, pp. 48-96.

The polyester can include one or more non-ester linkages in the mainpolymer chain which can be configured susceptible to cleavage in vivo.Suitable non-ester linkages may include amides, urethanes, carbonates,iminocarbonates, oxalates, oxamates, orthoesters, anhydrides,phosphazenes, glycosides, and ethers. Incorporation of such linkages canbe used to alter biodegradation rates, tailor mechanical, surface, orother properties of the polymer, improve processing and handling of thematerials, and/or to provide methods for attachment of other compoundsto the polymers (e.g., contrasting or treatment agents described below).

A typical polymer suitable for fabricating bladder 12 can include:D,L-polylactide, lactide-glycolide copolymers, PEG-PLA copolymers, andpolyesters and polyamides and other biodegradable compositions that forma strong film that can maintain an expanded state for extended timeperiods.

The time required for a polymer to degrade can be defined by selectingappropriate monomers. Differences in crystalline structure also alterdegradation rates. Actual mass loss initiates when the polymer matrixdegrades to oligomeric fragments that are small enough to be watersoluble. Hence, initial polymer molecular weight influences thedegradation rate. Degradable polymers containing water-soluble polymerelements have been previously described, see, for example, Sawhney etal., (1990) “Rapidly degraded terpolymers of dl-lactide, glycolide, andε-caprolactone with increased hydrophilicity by copolymerization withpolyethers,” J. Biomed. Mater. Res. 24:1397-1411. Degradation rate andthus polymer selection is determined according to the use of device 10.For example, during cryotherapy and thermal ablation a polymer with adegradation time period of a few hours to one or two weeks is selected,during external beam radiation a polymer with a degradation time periodof 5 to 6 weeks is selected, while during brachytherapy a polymer with adegradation time period of a few months is selected.

It will be appreciated that permanent implantation (preferably of adegradable device) is particularly useful in that it enables multipletreatment sessions without having to repeatedly insert and position atissue protecting device. A device designed capable of such permanentimplantation is particularly useful in cases where a treated individualis subjected to several treatment sessions (e.g., radiation) over anextended time period (e.g. weeks). In such a case, repeated implantationof a tissue protective device and thus repeated discomfort to theindividual can be avoided by using device 10 of the present invention.

As is mentioned hereinabove, device 10 displaces or separates one tissuefrom another when bladder 12 is expanded.

Bladder 10 can be expanded using one of several approaches. To enableexpansion, device 10 preferably includes a port 14 through which bladder12 can be expanded or collapsed. Port 14 is preferably a small diameterport with a diameter which is ⅕ to 1/100, preferably ⅕ to 1/20 of theexpanded thickness or width of expanded bladder 12. Port 14 can be afluid filling port, in which case bladder 12 can be expanded by using agas or a liquid and collapsed via emptying. Alternatively, port 14 canbe utilized to introduce a solid yet elastic element that can fillbladder 12 such that it assumes a semi rigid expanded state. As is shownin FIG. 1 d, such a solid element can be, for example, an elongatedmember 15 (e.g. a wire or thread 3-5 mm in diameter) that can be forcedinto a linear state 17 and thus can be introduced into bladder 12through port 14, but when released naturally assumes a coiled structure19 that forces bladder 12 to assume an expanded state. Such a wire canhave a circular, elliptic, triangular rectangular or stellate profileand can be solid or hollow. The profile can be uniform along the entirelength of the wire or it can change intermittently in order to permiteasier folding inside bladder 12. Bladder 12 can also be filled withbeads that can optionally be interconnected by a thread or wire. It willbe appreciated that such wire or bead expansion traverses the need forbladder sealing. Elongated member 15 can be made from a biocompatibleand optionally biodegradable elastic material such as, for example,polylactide, poly(lactide-glycolide), poly(lactide-caprolactone) andpolycaprolactone or a Shape Memory Polymer (SMP) made for example frommulti block copolymers of lactide and caprolactone which can assume anelongated state when heated and a coiled state when cooled to bodytemperature.

Although any of the above approaches can be effectively utilized toexpand/collapse bladder 12, liquid expansion is presently preferred forits added benefits and ease of use.

Use of a liquid provides several advantages. It enables bladder 12 toconform to the tissue displaced and thus apply uniform pressurethereupon. It enables introduction of useful agents, such as contrastingagents or treatment agents into bladder 12 and it can serve as anexcellent physical barrier against heat, or radiation by introducingsubstances that absorb radiation such as iodinated agents orfluorocarbons.

Any liquid can be utilized to expand bladder 12, preferably the liquidutilized is biocompatible and physiological such as 0.9% saline, Ringersolution or Hartman solution. Use of a physiological liquid isparticularly advantageous in that it provides a good sonographic windowwhich is essential in procedures that necessitate ultrasound guidancefor introduction of the balloon or for local therapy or follow up (e.g.trans rectal ultrasound for therapy of the prostate). Additionally, incase of side effects such as pain or discomfort or local infection theballoon can be easily collapsed using a thin needle.

In the liquid expansion configuration, bladder 12 is preferablyconstructed from a fluid impermeable material such that an expandedstate thereof can be retained following filling. Examples of suitableliquids include, but are not limited to, water, saline and the like.

As is mentioned above, the liquid can include agents that can be usefulin imaging, radiation and/or thermal treatment modalities.

For example, to enhance imaging, the liquid in bladder 12 can includeimaging contrast agents such as iodinated or baritated substances orvarious fluorocarbons, which are useful in fluoroscopy or CT scanning;echogenic or anechoic substances which are useful in ultrasound imaging,MRI contrasts agents such godolinium, radioactive isotopic substancesfor SPECT, or PET scanning. To protect tissue from radiation, agentssuch as iodinated substances, baritated substances, fluorocarbons, andthe like can be included in the liquid. Agents active in tissuehealing/repair can also be added to the liquid in which case, bladder 12is preferably constructed so as to enable release of such agents to thetissue. It will be appreciated that the above described agents canalternatively be added or incorporated into the material of bladder 12in which case, such agents can be released upon degradation of device10, or following absorption of a dose of treatment (e.g., radiation).

Port 14 can be constructed with a plurality of channels so as to enablecirculation of a liquid with expanded bladder 12. Such circulation ofliquid enables tissue cooling or heating when necessary. For example,when thermal ablation is conducted, cooling of non-treated tissue can beeffected via circulation of cold water. It will be appreciated that insuch cases, bladder 12 is preferably constructed such that the cooledside (facing non-treated tissue) is more thermally conductive then theside of bladder 12 facing treated tissues.

Port 14 can include additional channels that enable introduction of aviewing device such as endoscope or an ultrasonic transducer, which canbe to assess the effect of treatment, or to introduce therapeutic probessuch as radiofrequency, or high intensity ultrasound probe or tointroduce optical fibers which can be used for probing or fortransillumination.

It will be appreciated that various gelling liquids can also be utilizedto expand bladder 12. Such gelling liquids can be used to furtherenhance the tissue protective qualities of bladder 12 by providing aphysical cushion capable of further protecting the displaced/separatedtissue from physical trauma which can result from displacement ortreatment. Gelling materials are also advantageous in that in case ofrupture, the gel will be locally retained and will not dissipate.Examples of gelling liquids that can be utilized to expand device 10 ofthe present invention include, but are not limited to, absorbablehaemostatic agents such as, gelatin, cellulose, bovine collagen andbiodegradable synthetic adhesives such as, poly ethylene glycol (PEG).

The liquid utilized to expand bladder 12 can also include a fluorophoreor any other trans-illuminative substance which can emit or reflectlight which can be used to guide a procedure performed on the treatedtissue. Alternatively such a light reflecting/emitting substance can beincorporated into the material of bladder 12.

As is mentioned hereinabove, device 10 of the present invention ispreferably inserted and positioned within tissue using a guide.

Thus, according to another aspect of the present invention there isprovided a system which can be utilized for tissue displacement orseparation.

Such a system includes device 10 and a guide which is detachablyattached to device 10. The guide serves to insert and position device 10and to expand bladder 12 when in position.

The guide can be a thin catheter or a blunt tip needle (canula), ofabout 1-5 mm in diameter, preferably 2-3 mm in diameter. The guideposses a lumen through which a bladder-expanding fluid (or rigidelement) can be conducted from a device such as a syringe (in the caseof fluid) to bladder 12. Bladder expansion can be monitored by usingdifferent imaging technique such as: direct view, transillumination,fluoroscopy, endoscopic or laparoscopic US, US, CT scan, MRI, endoscopicview, etc. The guide is preferably constructed from biomedical gradeelastomer such as PVC or polyurethane.

In cases where device 10 is left within the body, the guide is detachedfrom the device 10 which preferably remains inflated by self sealing ofport 14. Such self-sealing can be effected by a one way valveincorporated into port 14, by viscosity of a bladder expanding liquid(e.g. one that forms a gel) or by a biodegradable sealing mechanism suchas that described below with respect to FIG. 1 e. A cutting cathetermade from bio-compatible material and having a sharp edge may be used todetach device 10 from the guide if necessary.

FIG. 1 e illustrates one embodiment of the system for tissuedisplacement or separation which is referred to herein as system 100.System 100 includes device 10 which is shown in a collapsed (rolled)state. System 100 also includes a guide 20 which includes a needle 22for attaching to port 14 of device 10, a packaging sheath 28 for holdingdevice 10 and a dilator sheath 26 for holding packaging sheath 28.

Needle 22 and dilator sheath 26 are used in a manner similar to the wellknown Seldinger technique (The Seldinger technique. Reprint from ActaRadiologica 1953; AJR Am J. Roentgenol. 1984 January; 142(1):5-7). Thisminimally invasive technique is used to provide a device or substanceaccess to a specific location in the body through a dilator sheath.Thus, positioning of dilator sheath 26 within a body tissue enabledelivery of device 10 (rolled or folded inside packaging sheath 28) to aspecific body location. Once positioned, device 12 is deployed byretracting both sheaths and expanding bladder 12 (via for examplesyringe connected to port 34 of needle 22) at the proper location andorientation. Device 10 is then sealed to prevent deflation by using theone way valve or self sealing mechanism described above. Alternatively,port 14 of device 10 can be sealed by using a biodegradable plug 30which is forcefully stuck into a non resilient biodegradable tube 32attachable at port 14. Alternatively, sealing can be performed byexternal compression of port 14 with an elastic constricting ring or byknotting of port 14.

When used in long term procedures, needle 22 of guide 20 is detachedfrom expanded and sealed device 10 and removed from the body, otherwise,following procedure, needle 22 with attached device 10 are removed fromthe body along with dilator sheath 26 and packaging sheath 28.

Examples 3-8 of the Examples section which follows describe use ofsystem 100 in several treatment procedures.

Thus, the present invention provides a device and system which can beutilized in protecting tissue from the harmful effects of treatment. Asis described herein, one of the notable features of the present deviceis its ability to uniformly displace/separate tissues in a manner whichminimizes tissue damage, while being implantable and optionallybiodegradable thus enabling repeated treatment to a tissue regionwithout necessitating repeated in-tissue positioning procedures.

As used herein the term “about” refers to +10%.

Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following examples, which are not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds support in the following examples.

EXAMPLES

Reference is now made to the following examples, which together with theabove descriptions, illustrate the invention in a non limiting fashion.

Example 1 Bladder Fabrication

An important feature of the bladder of the present device is its abilityto retain a predetermined shape once expanded. This feature is criticalfor optimal tissue displacement/separation and minimization of localizedtissue pressure. For the same reason, the bladder of the present deviceis preferably fabricated with a smooth seamless external surface. Tofacilitate these requirements, a unique production process wasformulated. The process combines two production concepts, a permutationof “lost wax” casting and dip molding.

Dip molding is used to “build” the bladder walls by dipping a pre-shapedmodel of the bladder in a solution made of a polymer dissolved inorganic solvent. The pre-shaped model is made of materials that arelater extracted from the internal volume of the bladder through itsorifice. Unlike the well known “lost wax” casting method, wax cannot beused since it dissolves in organic solvents such as alcohols,chlorinated hydrocarbons, alkanones, acetonitrile, dialkyl ethers,cyclic ethers, acetate alkyl esters, and common aromatic solvents.Typical solvents include butanol, dichloromethane, chloroform, butanone,acetone, acetonitrile, disiopropyl ether, tetrahydrofurane, dioxane,ethyl and butyl acetate, and toluene. The only casting agents that canbe used are hydrophilic in nature and include protein, polysaccharidesand various synthetic and semisynthetic polymers. Examples include, butare not limited to, gelatin, agar, alginate, hydroxypropylcellulose,poly(acrylic acid-co-methylmethacrylate), chitosan, dextran, andarabinogalactane.

Alternatively, alloys with a low melting temperature (e.g., alloysincluding rare earth metals) can be used for the casts. These casts areheated and melted and extracted at a temperature lower than the meltingtemperature of the coating polymer.

The bladder shape is based on the anatomy of the target location and isdesigned to achieve an optimal separation with minimal local pressure onthe surrounding tissues/organs.

The following provides a stepwise description of the bladder productionprocess of the present invention.

(i) Prepare mold of the required bladder shape.

(ii) Inject hot casting agent (10% W/V agar in water) and wait 15minutes for the cast to cool down and harden.

(iii) Extract bladder model from mold and attach to dip molding handle(See FIG. 2).

(iv) Dip the model inside the dipping solution (e.g. 10% W/Vbiodegradable polymer dissolved in an organic solvent) at a constantspeed (˜20 cm/min.)

(v) Repeat step (iv) several (e.g. six) times until required coatingthickness is acquired.

(vi) Wait until organic solvent evaporates (2-3 hours).

(vii) Extract casting agent through bladder orifice by heating the modeland washing with water.

It will be appreciated that when the bladder is filled with abiodegradable fiber, it can be alternatively fabricated by welding orgluing together of two films of the bladder material. “Pressureforming”, “film extrusion” or “blown film” methods are used to preparethe films. The films are then welded along the bladder external pathusing an accurate and controlled ultrasonic energy or glued using anaccurate deposit of organic solvent along the gluing path.

Example 2 Prostate Cancer

Prostate cancer is the most common malignancy in men; 220,000 new casesare diagnosed each year in US and 50,000 patients undergo radicalprostatectomy each year in the U.S. During the last few years there isan increasing trend to perform this surgery via minimally invasivetechniques such as laparoscopic radical prostatectomy.

In radical prostatectomy (using either the open or the laparoscopicapproach), the device of the present invention is inserted into thespace between the rectum and prostate (see FIG. 3 a) using thetransperineal approach which is guided by trans-rectal ultrasound.Initially a thin 22 to 18 gauge needle is introduced into this spaceunder trans-rectal ultrasound guidance and this virtual space isenlarged by injecting 5 to 20 cc of physiological liquid such as, forexample, 0.9% sterile saline. A guide wire is inserted through theneedle into this space; the needle is removed and a dilator is used toenlarge the tract; an introducer sheath is passed over the dilator andthe dilator and the guide wire are removed; the folded device with itssheath measuring between 2 and 3 mm in diameter are introduced throughthe introducer sheath and the bladder component is deployed and expandedin the space between the rectum and prostate in the proper orientation.A pear shaped non distensible bladder 3 to 5 cm length, 3 to 5 cm widthand 1 to 2 cm height (see FIGS. 3 b-c) is preferably used. Uponexpansion with either a biodegradable material or physiologicalsolution, the bladder thickness will range between 10 to 20 mm. Aspecific bladder size corresponding to the size of the prostate in thatparticular patient will be used. Thereafter, an optic fiber can beintroduced into the bladder through the needle and the needle can beremoved. During the dissection of the prostate from the rectum theoptical fiber is used for illumination and the inflated space betweenthe rectum and prostate is viewed through the laparoscope bytransillumination. Using such an approach, the borders of the prostatecan be clearly seen and the prostate can be safely and rapidly dissectedfrom the rectum and from the erectile nerves laying on the rectal side.In such a procedure, the device bladder is preferably filled with a gel,in which case puncturing of the bladder wall with a surgical instrumentor damage thereto caused by thermal energy will not lead to loss oftissue displacement. Following the procedure, the bladder and the gelare removed using suction and laparoscopic instruments.

Approximately 100.000 patients undergo prostate radiotherapy in the U.S.each year. Half of these cases are performed via external beam radiationand the other half via brachytherapy. In prostate irradiation, thedevice of the present invention is preferably a pear shaped bladder 3 to5 cm in length, 3 to 5 cm in width and 1-2 cm in thickness whenexpanded. The bladder is inserted into the correct space between therectum and prostate as described above under local anesthesia. Thebladder is then deployed and filled with physiological liquid or gel toits final dimensions and in the proper orientation. The catheter is thendetached from the inflated bladder and the bladder is sealed in order toprevent deflation. Such sealing may be performed by using abiodegradable plug as described above or by tying of the biodegradablefeeding tube. The bladder is sealed for the duration of the radiationtherapy thus preventing its collapse. Patients undergo 30 to 40 sessionsof radiation to the prostate 70 to 84 Gy on an ambulatory basis over aperiod of 5 to 6 weeks. Therefore, the bladder and/or the gel are chosenin such way so as to degrade following this period of time. Moreover, aradiation barrier in the form of a iodinated substance or fluorocarbonsmight be introduced into the bladder and/or the gel in order to furtherreduce exposure of the rectal wall, erectile nerves and bladder base toradiation and therefore permit use of a higher radiation dose (e.g. morethan 80 Gy or 8000 rads). A radiotracer can optionally be used in orderto enable delineation of the prostate during radiotherapy. The urinarybladder and external urinary sphincters can be additionally protected byusing additional spacers on the anterior surface of the prostate at itsbase and between the sphincter and prostate apex. Moreover, since thesespacers compress the prostate and separate adjacent tissues, therespiratory movements of the prostate are reduced permitting a moreaccurate dose delivery to the prostate.

The device of the present invention can also be used in prostate cancercryotherapy. In such cases, a transperineally positioned device havingthermal insulation and additional ports for hot water circulation or adevice provided with thermal inducible means is utilized. In the lattercase, the device can incorporate a thermal inducible gel or carbonparticles that can be heated via a remote radiofrequency source situatedin the rectal lumen for example, or by using a magnetic field.

A similar device can be used in thermal ablation treatment of prostatetumors or benign hyperplasia of the prostate. In such cases,intermittent or continuous liquid circulation might be used for coolingthe rectal wall and erectile nerves. Additionally, when using a spacerbladder a heat reflective coating on the side facing the prostate mightbe used to reflect the radiation energy away from the rectum and backtowards the prostate.

Example 3 Cholelithasis

Tissue displacement can also be performed during laparoscopiccholecystectomy. Approximately 400.000 such cases are performed eachyear in U.S. mostly for cholelithasis.

In cholecystectomy the bladder is preferably an elongated (5 to 7 cmlong, 3 to 5 cm wide and 1 to 2 cm thick) shape (See FIGS. 4 b-c). Thedevice is preferably introduced between the gallbladder and liver inorder to separate these organs and facilitate dissection (see FIG. 4 a).

The bladder is folded in an encasing sheath and connected to a feedingcatheter and the device is introduced through a 5 mm port within theperitoneal cavity. Initially minimal hydro-dissection is performedbetween these organs to create a space, then the device folded withinthe encasing sheath is introduced into this space, the sheath is removedand the bladder is expanded with a liquid or a gel. The catheter is thendetached from the expanded bladder and the bladder is sealed in order toprevent deflation. Catheter detachment enables introduction of surgicalinstruments through the catheter port and dissection of the gallbladderfrom the liver. Use of a haemostatic agent such as fibrin, thrombin,alginate, gelatin or cyanacrylate (optionally incorporated into thebladder) enables homeostasis of the bleeding regions.

Example 4 Large Bowel Tumors

Tissue displacement can also be performed during laparoscopic colectomy.Approximately 300.000 such cases are performed each year in USA mostlyfor large bowel tumors.

In colectomy an elongated bladder 10 to 20 cm long, 3 to 7 cm wide and1-3 cm thick (when expanded) is preferably used (see FIGS. 5 b-c). Thebladder in its encasing sheath is introduced between the right colon andretroperitoneum or between the left colon and retroperitoneum or betweenthe rectum and sacrum or rectum and urinary bladder in order to separatethese tissues and facilitate dissection (see FIG. 5 a). Initiallyminimal hydro-dissection is performed between these organs to create aspace, then the device in its encasing sheath is introduced within thisspace, the sheath is removed and the bladder is expanded using a liquidor a gel in the proper orientation.

The catheter is then detached from the expanded bladder and the bladderis sealed in order to prevent collapse. Catheter detachment enablesintroduction of surgical instruments through the catheter port anddissection of tumor tissue.

Example 5 Cancer of the Uterine Cervix

Cancer of the uterine cervix is one of the most common tumors in women,accounting for more then 100,000 of cases annually in the U.S. Most ofthese cases are treated by cavitary radiation therapy. During thistherapy, radiation may injure the rectum, bladder and small bowels.

The device of the present invention is inserted between the rectum andposterior vaginal wall/uterine cervix through posterior vaginal wall orthrough the perineum (see FIG. 6 a) under trans rectal or trans vaginalultrasound guidance. An extension of the bladder into the Douglas pouchor an additional device may be provided to push up the bowels. Thefolded device and sheath measuring between 2 and 3 mm in diameter areintroduced through the introducer sheath and the bladder is deployed andexpanded in the proper orientation in a space created (as describedabove) between the rectum and vagina/uterine cervix. An elongatedbladder 3 to 10 cm in length, 3 to 5 cm in width and having a variable(expanded) thickness of 1 cm in the inter-rectal vaginal space to 5 cmin the distal Douglas pouch position (see FIGS. 6 b-e).

The catheter is then detached and the bladder sealed as described above.Radiation therapy is then administered. Patients with Stage IB to IVBsquamous cell carcinoma of the cervix (staging determined according tothe International Federation of Gynecology and Obstetrics) are treatedwith a combination of external beam radiotherapy (EBRT) and high-doserate intracavitary brachytherapy (HDR-ICBT). For patients withearly-stage disease, 20 gray (Gy) of EBRT are delivered to the wholepelvis, followed by 24 Gy (in 4 fractions) of HDR-ICBT and 30 Gy ofcentral-shielding EBRT. For patients with advanced-stage disease, 20-40Gy of whole pelvic EBRT are administered, followed by 24 Gy (in 4fractions) of ICBT and 30-10 Gy of central-shielding EBRT. The overalltreatment time is approximately 6 weeks.

Example 6 Rectal Cancer

Rectal cancer is a common tumor accounting for 145,000 new cases eachyear in the U.S. alone. Thirty to forty percent of cases undergopreoperative or postoperative external beam irradiation. This treatmentmay cause injury to the urinary bladder, vagina and small bowels.

The device of the present invention is positioned between the urinarybladder and sacrum or between the rectum and urinary bladder (see FIG. 7a) with an extension or an additional device in the Douglas pouchthrough the perineum using trans rectal, trans vaginal ultrasoundguidance or CT guidance. An extension of the bladder into the Douglaspouch may be provided to push up the bowels. The folded device andsheath measuring between 2 and 3 mm in diameter are introduced throughthe introducer sheath and the bladder component is deployed and expandedin a space between the rectum and urinary bladder which is prepared asdescribed above. A elongated bladder of 3 to 10 cm in length, 3 to 5 cmin width and having a variable thickness (when expanded) of 1 cm in theintervesical-rectal space to 5 cm height in the distal Douglas pouchposition (see FIGS. 7 b-c) is used.

The catheter is then detached and the bladder sealed as described above.Radiation therapy is then administered, patients receive 45 Gy (4500rad) provided in fractions over 5 weeks with or without the addition ofneoadjuvant chemotherapy. Surgery is performed 4-6 weeks followingcompletion of the radiotherapy course. Radiotherapy can also beadministered following surgery in an adjuvant setting. In the lattercase, the prescribed radiation dose is 50.4 Gy which is provided in 28fractions.

Example 7 Pulmonary Tumors & Mediastinum Lymphomas

The device of the present invention can also be used during radiationtherapy to pulmonary tumors or to lymphomas situated in the mediastinum.In pulmonary tumors, the bladder is preferably positioned between thelung and mediastinum containing: great blood vessels, heart, spine withthe spinal cord, and lymphatic vessels and nodes, in order to separate apossible medial tumor from healthy tissues. In lymphomas, the device ispreferably positioned between the enlarged lymph nodes situated in thesuperior mediastinum and the heart and great vessels, spine and lungtissue. The device is preferably positioned under CT guidance. Thebladder is preferably 5 to 10 cm in length; 3 to 5 cm in width and 1 to2 cm in thickness when expanded (see FIGS. 8 b-c). A number of smallersized bladders can also be used to efficiently cover this complex space.

The folded device with its sheath measuring between 2 and 3 mm indiameter are introduced through the introducer sheath and the bladdercomponent is deployed and inflated in the mediastinal space (see FIG. 8a) in the proper orientation.

The catheter is then detached and the bladder sealed as described above.In case of pulmonary tumors radiotherapy is administered as either 45 Gyover 15 sessions up to 70 Gy over 70 sessions over a period between 3 to10 weeks according to type of tumor and stage. Such radiation therapy istypically administered in combination with chemotherapy. In case ofmediastinal lymphomas chemotherapy is administered followed byconsolidation radiotherapy at a dose of 36 Gy over 4 to 6 weeks to bulkymediastinal disease.

Example 8 Breast Cancer

Another application may be for radiation treatment of breast cancer.This tumor is the most prevalent tumor in women account for 300.000 newcases in US every year. Most patients undergo lumpectomy. In themajority of cases irradiation is given to the nearby breast tissue andcase of tumors situated near the chest wall the thoracic wall and lungreceive a significant dose of irradiation.

The folded device and sheath measuring between 2 and 5 mm in diameterare introduced through the introducer sheath and the bladder componentis deployed and expanded in the space between the breast and abdominalwall (see FIG. 9 a). A circular flat bladder 5 to 15 cm in diameter, and1 to 3 cm in thickness (see FIGS. 9 b-c) is preferably used in thisprocedure.

The catheter is then detached and the bladder sealed as described above.Radiation therapy is then administered. The standard technique ofradiotherapy (RT) following breast conserving surgery (BCS) is to treatthe entire breast up to a total dose of 45-50 Gy with or without tumorbed boost; typical treatment includes 30 sessions which are administeredover a period of six weeks.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1-38. (canceled)
 39. A medical device for insertion into a patient'sbody between target tissue to be subjected to a radiation, thermal ordrug treatment, and adjacent tissue adjacent to said target tissue, saidmedical device comprising: an expandable bladder expandable from anormal condition for insertion into the patient's body between saidtarget tissue and said adjacent tissue, to an expanded condition forspacing said adjacent tissue from said target tissue; said expandablebladder being of a material, size and configuration such that, in itsexpanded condition, it effectively spaces said adjacent tissue from saidtarget tissue and effectively protects said adjacent tissue during saidradiation, thermal or drug treatment of the target tissue, and therebyenables maximizing said treatment of the target tissue while minimizingthe effect of such treatment on said adjacent tissue.
 40. The medicaldevice according to claim 39, wherein said radiation, thermal or drugtreatment is an extensive time-period treatment, said expandable bladderbeing of a biodegradable material to enable it to be left in thepatient's body so as to be effective for said extensive time-period oftreatment, and thereafter to be absorbed by the patient's body.
 41. Themedical device according to claim 40, wherein said expandable bladderincludes an inflation port for inletting an inflating fluid, and abiodegradable plug for closing said inflation port after the bladder hasbeen inflated.
 42. The medical device according to claim 40, whereinsaid expandable bladder includes an inflation port for inletting aninflating fluid, and a biodegradable plug for closing said inflationport after the bladder has been inflated.
 43. The medical deviceaccording to claim 40, wherein said treatment is a prostate cancertreatment, and said expandable bladder is of a size and configurationsuch that in its expanded condition it corresponds to the size andconfiguration of the prostate being treated.
 44. The medical deviceaccording to claim 43, wherein said expandable bladder is, in itsexpanded condition, of a pear-shaped configuration, having a length of3-5 cm, and width of 3-5 cm, and a thickness of 1-2 cm.
 45. The medicaldevice according to claim 40, wherein said treatment is a uterine cervixcancer treatment, and said expandable bladder is of a size andconfiguration in its expanded condition corresponding to the canceroustissue of the uterine cervix being treated.
 46. The medical deviceaccording to claim 40, wherein said treatment is a rectal cancertreatment, and said expandable bladder is of a size and configuration inits expanded condition corresponding to the cancerous tissue of therectum being treated.
 47. The medical device according to claim 40,wherein said treatment is a pulmonary tumor treatment, and saidexpandable bladder is of a size and configuration in its expandedcondition corresponding to the pulmonary tumor being treated.
 48. Themedical device according to claim 40, wherein said treatment is amediastinum lymphomas treatment, and said expandable bladder is of asize and configuration in its expanded condition corresponding to themediastinum lymphomas being treated.
 49. The medical device according toclaim 40, wherein said treatment is a breast cancer treatment, and saidexpandable bladder is of a size and configuration in its expandedcondition corresponding to the breast cancer tissue being treated. 50.The medical device according to claim 39, wherein said expandablebladder is expandable by a physiological solution introduced therein,and is of a configuration such that in its expanded condition it appliesa substantially uniformly-distributed pressure between said targettissue and said adjacent tissue.
 51. The medical device according toclaim 39, wherein said treatment is a radiation treatment, and saidexpandable bladder is expanded by, or includes, a radiation-shieldingliquid effective to shield said adjacent tissue during a radiationtreatment of said target tissue.
 52. The medical device according toclaim 39, wherein said treatment is a thermal treatment, and saidexpandable bladder is expanded by, or includes, a thermally-insulatingmaterial.
 53. The medical device according to claim 39, wherein saidtreatment is a chemical or drug treatment, and said expandable bladderis of a chemically-resistant or drug-resistant material effective toprotect said adjacent tissue during the chemical or drug treatment ofsaid target tissue.
 54. The medical device according to claim 39,wherein said expandable bladder is in a flat rolled state in its normalcondition to facilitate its insertion into the patient's body.
 55. Themedical device according to claim 39, wherein said expandable bladder isformed with an irregular outer surface to resist its displacement afterit is inserted and expanded between the target tissue and the adjacenttissue.
 56. The medical device according to claim 39, wherein saidexpandable bladder includes an adhesive coating on its outer surface toprevent its displacement after it is inserted between the target tissueand adjacent tissue.
 57. The medical device according to claim 39,wherein said expandable bladder is expanded by introducing therein anelongated elastic element having an initially non-expanded state and anormally coiled state to expand the bladder when received within it. 58.The medical device according to claim 39, wherein said expandablebladder is expandable by a liquid which includes an image-enhancingagent, a heat-absorbing agent, or a radiation-absorbing agent.
 59. Themedical device according to claim 39, wherein said expandable bladder isexpandable by a liquid circulated therethrough for heating or coolingsaid adjacent tissue.
 60. The medical device according to claim 39,wherein said expandable bladder is expandable by a gelling liquideffective to solidify and seal the bladder in its expanded state. 61.The medical device according to claim 39, wherein said medical devicefurther includes a guide and a guiding system for guiding the insertionof the expandable bladder in its normal condition into the patient'sbody between said target tissue and said adjacent tissue.
 62. Themedical device according to claim 39, wherein said expandable bladder isa seamless bladder.
 63. The medical device according to claim 61,wherein said seamless bladder has an inflation port which is of adiameter 20% or less the largest diameter of the bladder in its expandedcondition.
 64. A medical device for insertion into a patient's bodybetween target tissue to be subjected to a medical treatment, andadjacent tissue adjacent to said target tissue, said medical devicecomprising: an expandable bladder expandable from a normal condition forinsertion into the patient's body between said target tissue and saidadjacent tissue, to an expanded condition for spacing said adjacenttissue from said target tissue; said expandable bladder being of amaterial, size and configuration such that, in its expanded condition,it effectively spaces said adjacent tissue from said target tissue andeffectively protects said adjacent tissue during said medical treatmentof the target tissue, and thereby enables maximizing said treatment ofthe target tissue while minimizing the effect of such treatment on saidadjacent tissue; wherein said treatment is a prostate cancer treatment,and said expandable bladder is of a size and configuration such that inits expanded condition it is of pear-shape, has a length of 3-5 cm, awidth of 3-5 cm, and a thickness of 1-2 cm, to correspond to the sizeand configuration of the prostate being treated.
 65. A method ofadministering a radiation, thermal or drug treatment to a target tissuewithin a patient's body, comprising: inserting into the patient's body,between said target tissue and adjacent tissue adjacent to said targettissue, an expandable bladder expandable from a normal condition to anexpanded condition for spacing said adjacent tissue from said targettissue; expanding said expandable bladder; and administering saidradiation, thermal or drug treatment to said target tissue; saidexpandable bladder being of a material, size and configuration such thatin its expanded condition, it effectively spaces said adjacent from saidtarget tissue and effectively protects said adjacent tissue during saidradiation, thermal or drug treatment of the target tissue, and therebyenables maximizing said treatment of the target tissue while minimizingthe effect of said treatment on said adjacent tissue.
 66. The methodaccording to claim 65, wherein said medical treatment is a radiationtreatment, and said expandable bladder is expanded by, or includes, aradiation-shielding liquid effective to shield said adjacent tissueduring the radiation treatment of said target tissue.
 67. The methodaccording to claim 65, wherein said medical treatment is a thermaltreatment, and wherein said expansible bladder is expanded by, orincludes, a thermally-insulating material.
 68. The method according toclaim 65, wherein said medical treatment is a chemical or drugtreatment; and said expansible bladder is of a chemically-resistant ordrug-resistant material effective to protect said adjacent tissue duringthe chemical or drug treatment of said target tissue.
 69. The methodaccording to claim 65, wherein said radiation, thermal or drug treatmentis an extensive time-period treatment, and said expandable bladder is ofa biodegradable material to enable it to be left in the patient's bodyso as to be effective for said extensive time-period of treatment, andthereafter to be absorbed by the patient's body.
 70. The methodaccording to claim 65, wherein said expandable bladder includes aninflation port for inletting an inflating fluid, and a biodegradableplug for closing said inflation port after the bladder has beeninflated.
 71. The method according to claim 65, wherein said treatmentis a prostate cancer treatment, and said expandable bladder is of a sizeand configuration such that in its expanded condition it corresponds tothe size and configuration of the prostate being treated.
 72. The methodaccording to claim 65, wherein said treatment is a uterine cervix cancertreatment, and said expandable bladder is of a size and configuration inits expanded condition corresponding to the cancerous tissue of theuterine cervix being treated.
 73. The method according to claim 65,wherein said treatment is a rectal cancer treatment, and said expandablebladder is of a size and configuration in its expanded conditioncorresponding to the cancerous tissue of the rectum being treated. 74.The method according to claim 65, wherein said treatment is a pulmonarytumor treatment, and said expandable bladder is of a size andconfiguration in its expanded condition corresponding to the pulmonarytumor being treated.
 75. The method according to claim 65, wherein saidtreatment is a mediastinum lymphomas treatment, and said expandablebladder is of a size and configuration in its expanded conditioncorresponding to the mediastinum lymphomas being treated.
 76. The methodaccording to claim 65, wherein said treatment is a breast cancertreatment, and said expandable bladder is of a size and configuration inits expanded condition corresponding to the breast cancer tissue beingtreated.
 77. The method according to claim 65, wherein said expandablebladder is a seamless bladder.
 78. The method according to claim 77,wherein said seamless bladder has an inflation port which is of adiameter 20% or less the largest diameter of the bladder in its expandedcondition.
 79. A method of forming a seamless bladder comprising: (a)providing a bladder template produced from material soluble in a firstliquid; (b) coating said template with a solution of a polymer insolublein said first liquid to thereby generate a polymeric coat on saidtemplate; and (c) exposing said template and polymeric film to saidfirst liquid thereby dissolving said template and releasing saidpolymeric film and forming the seamless bladder.
 80. The method of claim79, wherein said first liquid is a hydrophilic liquid.
 81. The method ofclaim 79, wherein said material soluble in a first liquid is gelatin oragar.
 82. The method of claim 79, wherein said polymer is selected fromthe group consisting of a poly(alkanoic acid), a polyorthoester, apolyphosphazene, a polyphosphate ester and a polyanhydride.
 83. Themethod of claim 82, wherein said poly(alkanoic acid) is selected fromthe group consisting of poly(lactic acid), poly(lactic acid-glycolicacid) and poly(lactic acid-caprolactone).